Response of human T lymphocyte lines to myelin basic protein: Association of dominant epitopes with HLA class II restriction molecules
✍ Scribed by Y. K. Chou; M. Vainiene; R. Whitham; D. Bourdette; C. H.-J. Chou; G. Hashim; H. Offner; A. A. Vandenbark
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- English
- Weight
- 978 KB
- Volume
- 23
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
In animals, the selection in vitro of T cell lines to myelin basic protein (MBP) can define immunodominant and encepbalitogenic epitopes which are preferentially associated with class I1 major histocompatibility (MHC) molecules. These principles were used to evaluate the specificity and MHC restriction of 14 human MBP-reactive T cell lines selected from normal individuals and patients with multiple sclerosis (MS) and other neurological diseases (OND). The four normal T cell lines recognized single, separate immunodominant MBP epitopes which were restricted by MHC molecules from the DR or in one case the DP class I1 locus. In contrast, the MS and OND T cell lines recognized multiple MBP epitopes, each in association with a discrete class I1 MHC molecule from the DR or DQ locus. Overall, HLA-DR molecules were used preferentially to associate with epitopes on human MBP, restricting 26/33 responses. As predicted from animal studies, T cells from genetically disparate individuals responded to different immunodominant epitopes on human MBP in association with distinct MHC class I1 molecules. HLA-DR2, which is overrepresented in MS patients, possessed an unusual capacity to restrict all eight epitopes identified on MBP in this study. These data provide the first evidence of genetically restricted human T cell recognition of potentially encephalitogenic epitopes of MBP.